Ji Yun Jeong

Quantitative CT analysis of pulmonary ground-glass opacity nodules for the distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma.

Objectives We aimed to analyze the CT findings of ground-glass opacity nodules diagnosed pathologically as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma in order to investigate whether quantitative CT parameters enable distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. Methods We reviewed CT images and pathologic specimens from 191 resected ground-glass opacity nodules with little or no solid component at CT. Nodule size, volume, density, mass, skewness/kurtosis, and CT attenuation values at the 2.5th–97.5th percentiles on histogram, and texture parameters (uniformity and entropy) were assessed from CT datasets. Results Of 191 tumors, 38 were AISs (20%), 61 were MIAs (32%), and 92 (48%) were invasive adenocarcinomas. Multivariate logistic regression analysis helped identify the 75th percentile CT attenuation value (P = 0.04) and entropy (P<0.01) as independent predictors for invasive adenocarcinoma, with an area under the receiver operating characteristic curve of 0.780. Conclusion Quantitative analysis of preoperative CT imaging metrics can help distinguish invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma.

Solitary Pulmonary Nodular Lung Adenocarcinoma: Correlation of Histopathologic Scoring and Patient Survival with Imaging Biomarkers

PURPOSE To evaluate the usefulness of histopathologic scoring for survival prediction in patients with solitary pulmonary nodular (SPN) lung adenocarcinomas and to correlate the histopathologic scoring with the results of computed tomography (CT) and fluorine 18 fluorodeoxyglucose positron emission tomography (PET)/CT. MATERIALS AND METHODS This retrospective study was institutional review board approved and the requirement for informed consent was waived. A total of 148 patients with SPN lung adenocarcinoma underwent PET/CT and CT. Correlations between histopathologic scores estimated by using two predominant histologic subtypes from each surgically resected specimen and the mass of the nodule at CT or maximum standardized uptake value (SUV(max)) at PET/CT were assessed. Disease-free survival (DFS) was estimated by using the Kaplan-Meier method, and the log-rank test was used to evaluate differences in each histopathologic subtype. RESULTS In 135 (91%) patients, tumors had a mixed subtype. The most frequently observed histologic subtypes, in decreasing order, were acinar (51%), lepidic (18%), solid (10%), and papillary (9%). DFS rates at 5 years were higher than 90% for the group of patients with nodules that showed the lepidic growth pattern, and 50% for patients with nodules that showed the micropapillary pattern. The pathologic score proved to be a significant predictor of DFS (P < .001). Both SUV(max) and the mass of the nodule were closely correlated with pathologic score. CONCLUSION Pathologic scoring appears to help predict DFS in patients with SPN lung adenocarcinoma and shows close correlation with imaging biomarkers including the mass of the nodule at CT and SUV(max) at PET/CT.

Favorable clinical outcomes of pemetrexed treatment in anaplastic lymphoma kinase positive non-small-cell lung cancer.

INTRODUCTION The development of anaplastic lymphoma kinase (ALK) inhibitor has just followed the recent discovery of ALK rearrangement in lung cancer, therefore not much is yet known about the clinical course and treatment outcomes to chemotherapy in ALK-positive patients. The purpose of this study was to investigate the clinical characteristics and treatment outcomes in patients with ALK-positive NSCLC treated with conventional chemotherapy during pre-ALK inhibitor period. PATIENTS AND METHODS We retrospectively screened 381 consecutive NSCLC patients without known epidermal growth factor receptor (EGFR) or KRAS mutation who were diagnosed between 2007 and 2008 at a single center, and identified ALK rearrangements by fluorescence in situ hybridization. Additional 44 ALK-positive patients who were identified since 2009 by central lab for participation on clinical trial were included for the analysis of clinical outcomes. RESULTS Of the 381 tumors screened, 21 (5.6%) showed ALK rearrangements, with twenty adenocarcinomas and one pleomorphic carcinoma. Of 65 ALK-positive patients including additional 44 ALK-positive patients, 32 patients received pemetrexed as a second- or further-line therapy, in whom the response rate was 34.4% (11/32), median progression-free survival (PFS) was 4.0 months (range: 0-22.0 months) and median overall survival (OS) was 50.8 months (95% confidence interval [CI]: 38.7-62.8). CONCLUSIONS The prevalence of ALK rearrangement was 5.6% among EGFR and/or KRAS wild-type/unknown NSCLC population. Pemetrexed, given as a second- or further-line therapy, showed favorable clinical outcomes in ALK-positive NSCLC patients.

Histopathology of lung adenocarcinoma based on new IASLC/ATS/ERS classification: prognostic stratification with functional and metabolic imaging biomarkers.

To correlate the results of histopathologic subtyping and grading of lung adenocarcinoma with maximum standardized uptake values (SUVmax) on positron emission tomography (PET)/computed tomography and apparent diffusion coefficient (ADC) values on diffusion‐weighted MRI (DWI).

Clinical impact of minimal micropapillary pattern in invasive lung adenocarcinoma: prognostic significance and survival outcomes.

Micropapillary subtype has recently been established to be a distinct marker for poor prognosis in lung adenocarcinomas. According to the current classification of lung adenocarcinomas, all subtypes are listed semiquantitatively in 5% increments. In other words, a minimal amount of the micropapillary pattern, precisely <5% of the entire tumor is disregarded. Therefore, we sought to assess the prognostic significance and survival outcomes in patients with a micropapillary pattern proportion of <5% of the entire tumor. A total of 525 patients with lung adenocarcinoma were classified into 3 subgroups according to the presence and proportion of micropapillary subtype: (1) ≥5% of the micropapillary pattern (n=114); (2) <5% of the micropapillary pattern (n=115); and (3) absence (<1%) of the micropapillary pattern (n=296). Sex, TNM stage, lymph node status (N status), tumor size, and predominant subtype demonstrated a significant difference among the 3 subgroups. Overall survival (OS) and disease-free survival (DFS) were significantly different among the 3 subgroups (P=0.009 and 0.001 for OS and DFS, respectively). Furthermore, OS was significantly better in patients without the micropapillary pattern (<1%) than in those with <5% (P=0.034). At multivariate analyses, age (P=0.005) and N status (P=0.005) were independent prognostic factors influencing OS. In conclusion, our results demonstrated that even a small proportion of the micropapillary pattern, specifically <5% of the entire tumor has a significant prognostic impact on OS. N status remained an independent prognostic factor that negatively influenced OS.

Quantitative image variables reflect the intratumoral pathologic heterogeneity of lung adenocarcinoma

We aimed to compare quantitative radiomic parameters from dual-energy computed tomography (DECT) of lung adenocarcinoma and pathologic complexity. A total 89 tumors with clinical stage I/II lung adenocarcinoma were prospectively included. Fifty one radiomic features were assessed both from iodine images and non-contrast images of DECT datasets. Comprehensive histologic subtyping was evaluated with all surgically resected tumors. The degree of pathologic heterogeneity was assessed using pathologic index and the number of mixture histologic subtypes in a tumor. Radiomic parameters were correlated with pathologic index. Tumors were classified as three groups according to the number of mixture histologic subtypes and radiomic parameters were compared between the three groups. Tumor density and 50th through 97.5th percentile Hounsfield units (HU) of histogram on non-contrast images showed strong correlation with the pathologic heterogeneity. Radiomic parameters including 75th and 97.5th percentile HU of histogram, entropy, and inertia on 1-, 2- and 3 voxel distance on non-contrast images showed incremental changes while homogeneity showed detrimental change according to the number of mixture histologic subtypes (all Ps < 0.05). Radiomic variables from DECT of lung adenocarcinoma reflect pathologic intratumoral heterogeneity, which may help in the prediction of intratumoral heterogeneity of the whole tumor.

Role of imaging biomarkers in predicting anaplastic lymphoma kinase-positive lung adenocarcinoma.

Objectives For the ultimately efficient screening of anaplastic lymphoma kinase gene (ALK)–positive cases, combination of radiometabolic characteristics with clinicopathologic features may be more useful. Therefore, we determined radiologic characteristics and metabolic characteristics in patients with adenocarcinoma harboring ALK mutations. Patients and Methods We retrospectively reviewed clinicopathologic CT and PET/CT data from patients with advanced lung adenocarcinoma screened for identifying ALK rearrangement. Lesion size, solidity, location, margins, CT attenuation, and SUVmax were assessed. Pathologic features such as differentiation, the presence of signet ring cell, EGFR/KRAS mutation status, and TTF-1 expression were also reviewed. Results Of the screened 221 patients, 41 patients (19%) demonstrated ALK rearrangements, and these individuals were younger than the ALK-negative patients (P < 0.001) and showed significant association with no exposure to tobacco (P = 0.028). ALK-positive lung adenocarcinomas were significantly less differentiated than those without rearrangements (P = 0.005). ALK-positive tumors showed significantly higher SUVmax than ALK-negative tumors (P = 0.016). Multivariate logistic regression modeling for predicting the ALK-positive lung adenocarcinoma disclosed that lower CT attenuation and higher SUVmax were significant independent factors of ALK rearrangements (odds ratio, 0.87 and 1.06; P = 0.03 and 0.01, respectively). Receiver operating characteristic analysis showed that the area under the receiver operating characteristic curve for SUVmax/CT attenuation ratio was 0.788, and the optimal cutoff value of SUVmax/CT attenuation ratio for identifying ALK-positive lung adenocarcinoma was greater than or equal to 0.208 (sensitivity, 74.2%; specificity, 81.0%). Conclusions This study shows that ALK-rearranged lung adenocarcinoma represents younger age, no history of smoking, the absence of spiculation on CT, and higher SUVmax/CT attenuation greater than or equal to 0.208 compared with those without ALK mutation.

Clinical significance of subclinical varicocelectomy in male infertility: systematic review and meta-analysis

Recent meta‐analysis by the Cochrane collaboration concluded that treatment of varicocele may improve an infertile couples chance of pregnancy. However, there has been no consensus on the management of subclinical varicocele. Therefore, we determine the impact of varicocele treatment on semen parameters and pregnancy rate in men with subclinical varicocele. The randomised controlled trials that assessed the presence and/or treatment of subclinical varicocele were included for systematic review and meta‐analysis. Random effect model was used to calculate the weighted mean difference of semen parameters and odds ratio of pregnancy rates. Seven trials with 548 participants, 276 in subclinical varicocelectomy and 272 in no‐treatment or clomiphene citrate subjects, were included. Although there was also no statistically significant difference in pregnancy rate (OR 1.29, 95% CI 0.99–1.67), surgical treatment resulted in statistically significant improvements on forward progressive sperm motility (MD 3.94, 95% CI 1.24–6.65). However, the evidence is not enough to allow final conclusions because the quality of included studies is very low and further research is needed.

Pathologic stratification of operable lung adenocarcinoma using radiomics features extracted from dual energy CT images

Purpose To evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment. Results Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i-uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514–1), 0.8610 (95% CI: 0.7547–0.9672), and 0.8394 (95% CI: 0.7045–0.9743), respectively. Materials and Methods A total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades. Conclusions Quantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma.

Dynamic prognostication using conditional survival analysis for patients with operable lung adenocarcinoma

Purpose To evaluate conditional survival among patients with surgically resected stage I-IIIa lung adenocarcinoma and identify changes in prognostic contributions for various prognostic factors over time. Patients and Methods We performed conditional survival analysis at each t0 (=0, 1, 2, 3, 4, 5 years) for 723 consecutive patients who underwent surgical resection for lung adenocarcinoma, stratified by various clinico-demographic features, as well as pathologic and imaging (tumor-shadow disappearance ratio [TDR] on CT and maximum standardized uptake value [SUVmax] on PET) characteristics. Uni- and multivariableCox regression analyses were performed to evaluate relationships between those variables and conditional survival. Results Three-year conditional overall survival (OS) and disease-free survival (DFS) were 92.12% and 75.51% at baseline, but improved steadily up to 98.33% and 95.95% at 5 years after surgery. In contrast to demographic factors, pathologic (stage, subtype, pathologic grade and differentiation) and radiologic factors (TDR and SUVmax) maintained a statistically significant association with subseqeunt 3-year OS until 3 years after surgery. According to the multivariableanalysis, high SUVmax and low TDR value were independent predictors of subsequent 3-year OS and DFS at baseline, 1 and 2 years after surgery, respectively. Conclusion Our findings based on CS provide theoretical background for clinicians to plan longer period of surveillance following lung adenocarcinoma resection in survivors with preoperatively high SUVmax and low TDR on PET-CT and chest CT, respectively.